1. Field of the Invention
This invention relates generally to an instrument using room-temperature sensors that measure magnetic susceptibility variations in the body. In particular, the instrument can monitor naturally occurring iron in a human liver noninvasively.
2. Discussion of the Related Art
Millions of people suffer from diseases related to the metabolism of iron in the human body. Among these are Cooley's anemia (also known as thalassemia), sickle cell anemia, and hemochromatosis. There is a strong need for an accurate, noninvasive method to measure body iron stores to enable more effective treatments.
This need is especially acute in the case of Cooley's anemia, or thalassemia. In this disease, where the blood is deficient in hemoglobin, patients must undergo blood transfusions in order to survive. These blood transfusions must be frequent (every 2 to 4 weeks). However, the repeated transfusions create a chronic iron overload with an abnormal buildup of iron in the liver, spleen, and heart, see Bothwell, T. H., et al., (1979); Iron Metabolism in Man, Oxford: Blackwell. This iron overload must be removed continually by chelation therapy, and iron stores must be monitored regularly to maintain the desired levels see Kontoghiorghes, G. J., et al. (1990), Long-term trial with the oral iron chelator 1,2-Dimethyl-3hydroxy-pyrid-4-one, Br. J. Hematology 76, 295; Nielsen, P., et al, (1995), Liver iron stores in patients with secondary hemosideroses under iron chelation therapy with deferoxamine or deferiprone, Br. J. Hematol. 91, 827; Olivieri, N. F., et al., (1995). Iron chelation therapy with oral deferiprone in patients with thalassemia major, New England J. Med. 332, 918.
Recent studies indicate that frequent blood transfusions can prevent the occurrence of strokes in children with sickle cell anemia and a clinical alert has been issued to US physicians, see NHLBI (1997), Press release of the National Heart, Lung, and Blood Institute: "New Treatment Prevents Strokes In Children With Sickle Cell Anemia." As with thalassemic patients, sickle cell anemic patients undergoing frequent blood transfusions suffer from liver iron overload.
Hemochromatosis afflicts a significant population (0.5% of the U.S. population with European ancestry) and results in excessive amounts of iron stored in the liver. The excess iron may be reduced by periodic blood withdrawals from the body. Monitoring iron stores is important to determine the well being of the patient and the course of treatment (such as the frequency of blood withdrawals).
At present, there is no truly satisfactory method for routinely monitoring iron stores. Serum ferritin and urine iron excretion measurements are not accurate, because they are only indirectly related to iron stores. Liver biopsy is painful and invasive, and thus unsuitable for routine monitoring. Nuclear resonance scattering techniques as taught in an article by Wielopolsky, L., and Zaino, E. C. (1992) entitled "Noninvasive in-vivo measurement of hepatic and cardiac iron," J. Nuclear Med. 33, 1278, is generally unsuitable because it involves high doses of a radioactive isotope. Computed tomography involves high doses of X-rays, and it is only sensitive enough to detect the highest levels of iron, see Guyader, Y., et al. (1989), Evaluation of computed tomography in the assessment of liver iron overload, Gastroenterology 97, 737.; and Nielsen, P., et al. (1992), Noninvasive liver-iron quantification by computed tomography in iron over loaded rats, Investigative Radiology 27, 312. Magnetic resonance imaging has been used to assess iron stores, but gives inaccurate results at the higher liver iron concentrations, see Kaltwasser, J. P., et al. (1990), Non-invasive quantification of liver iron overload by magnetic resonance imaging, Br. J. Hematology 74, 360; Engelhardt, R., et al. (1994), Liver iron quantification, Mag. Res. Imaging 12, 999.; and Nielsen, P., et al. (1995), Liver iron stores in patients with secondary hemosideroses under iron chelation therapy with deferoxamine or deferiprone, Br. J. Hematol. 91, 827.
Biomagnetic susceptometry is a diagnostic procedure that involves noninvasive, radiation-free, direct, and accurate, measurement of the magnetic susceptibility of organs and tissue within a human or animal body. Biomagnetic susceptometry can be used to measure human iron stores contained in the liver, see Harris, J. W., et al. (1978), Assessment of human iron stores by magnetic susceptibility measurements, Clin. Res. 26, 540A.; Brittenham, G. M., et al. (1993), Hepatic iron stores and plasma ferritin concentration in patients with sickle cell anemia and thalassemia major, Amer. J. Hematology 42, 85; Brittenham, G. M., et al. (1982), Magnetic susceptibility of human iron stores, New England J. Med., 307, 167 1.; Fischer, R., et al. (1992), Liver iron quantification in the diagnosis and therapy control of iron overload patients, Biomagnetism: Clinical. Aspects, M. Hoke, et al., eds., Elsevier, Amsterdam, p. 585., 1992; Fischer, R., et al. (1989), in Advances In Biomagnetism, S. J. Williamson, et al., eds., Plenum, New York, p. 501. Paulson. D. N., et al. (1991), Biomagnetic susceptometer with SQUID instrumentation, IEEE Trans. Magnetics 27, 3249.; and Nielsen, P., et al. (1995), Liver iron stores in patients with secondary hemosideroses under iron chelation therapy with deferoxamine or deferiprone, Br. J. Hematol. 91, 827. Unfortunately, the existing instruments, based on Superconducting Quantum Interference Devices(SQUIDs) are complex and expensive. They also use liquid helium, leading to significant operating costs and supply problems. Only a few such devices are in use worldwide presently due to their complexity and expense. These few instruments can serve only a tiny fraction of patients with iron-overload diseases. Thus, there is a need for a simpler, less expensive liver probing instrument using biosusceptometer concepts that can be installed in every major population center.
SQUIDs based on the recently developed High-Temperature Superconductors (HTS) could, in principle, reduce the cost of biomagnetic suceptomety. HTS SQUIDs, which can operate at liquid-nitrogen temperatures, would reduce operating costs, and some of the equipment costs, compared to SQUID devices operating at liquid helium temperatures. However, even at liquid-nitrogen temperatures, the operating costs would be higher than those of ordinary instruments operating at room temperature. Moreover, HTS-SQUIDs are expensive to construct and use, because of the difficulty and low yield of the fabrication process. The difficulties, and the costs, are compounded because these devices are vulnerable to moisture, thermal cycling, and static electrical discharge. HTS-SQUIDs also require the same expensive electronics as conventional SQUIDs.
The instant invention obviates the need for cryogenically cooled SQUIDs by providing operational use at room temperature, making for much less expensive fabrication and use. The invention allows, generally, for measurements of variations of magnetic susceptibility in a patient and, in particular, for an accurate and inexpensive way of monitoring liver iron in patients. In addition, certain improvements introduced in this invention are applicable to all types of magnetic susceptibility measurements.